Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity (original) (raw)
- Cell-Based Therapy
- Published: 17 February 2000
Cell-Based Therapy
Gene Therapy volume 7, pages 249–254 (2000)Cite this article
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Abstract
We have developed a culture method for the foreign serum-free generation of highly immunostimulatory, CD83+ human dendritic cells (DC). In this study, we evaluated the feasibility and consequences of endogenously expressing antigens in mature DC using adenoviral vectors. Transduction of DC with Ad-EGFP demonstrated endogenous fluorescence in 50–85% of CD83+ DC. Ad-transduced DC stimulated the proliferation of allogeneic CD8+ and CD4+ T cells at low DC: T cell ratios. However, at high DC: T cell ratios the stimulatory capacity of Ad-transduced DC was suppressed. This immunosuppressive effect was confirmed by demonstrating that the stimulatory function of untreated DC could be suppressed in a dose-dependent manner by addition of Ad-transduced DC. Furthermore, transwell experiments suggested that direct cell contact was required. Taken together, our results demonstrate the feasibility of efficiently expressing antigens in CD83+ DC using adenoviruses. However, immunosuppressive effects must be considered and carefully studied before Ad-transduced DC are employed for clinical trials.
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References
- Banchereau J, Steinman RM . Dendritic cells and the control of immunity Nature 1998 392: 245–252
Article CAS PubMed Google Scholar - Romani N et al. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability J Immunol Meth 1996 196: 137–151
Article CAS Google Scholar - Jonuleit H et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions Eur J Immunol 1997 27: 3135–3142
Article CAS PubMed Google Scholar - Schuler G, Steinman RM . Dendritic cells as adjuvants for immune-mediated resistance to tumors J Exp Med 1997 186: 1183–1187
Article CAS PubMed PubMed Central Google Scholar - van Elsas A et al. Peptide-pulsed dendritic cells induce tumoricidal cytotoxic T lymphocytes from healthy donors against stably HLA-A*0201-binding peptides from the Melan-A/MART-1 self antigen Eur J Immunol 1996 26: 1683–1689
Article CAS PubMed Google Scholar - Nestle FO et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells Nature Med 1998 4: 328–332
Article CAS PubMed Google Scholar - Tüting T, DeLeo AB, Lotze MT, Storkus WJ . Genetically modified bone marrow-derived dendritic cells expressing tumor-associated viral or ‘self’ antigens induce antitumor immunity in vivo Eur J Immunol 1997 27: 2702–2707
Article PubMed Google Scholar - Specht JM et al. Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases J Exp Med 1997 186: 1213–1221
Article CAS PubMed PubMed Central Google Scholar - Song W et al. Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity J Exp Med 1997 186: 1247–1256
Article CAS PubMed PubMed Central Google Scholar - Wan Y et al. Dendritic cells transduced with an adenoviral vector encoding a model tumor-associated antigen for tumor vaccination Hum Gene Ther 1997 8: 1355–1363
Article CAS PubMed Google Scholar - Gong J et al. Induction of antigen-specific antitumor immunity with adenovirus-transduced dendritic cells Gene Therapy 1997 4: 1023–1028
Article CAS PubMed Google Scholar - Perez-Diez A et al. Generation of CD8+ and CD4+ T-cell response to dendritic cells genetically engineered to express the MART-1/Melan-A gene Cancer Res 1998 58: 5305–5309
CAS PubMed Google Scholar - De Veerman M et al. Retrovirally transduced bone marrow-derived dendritic cells require CD4+ T cell help to elicit protective and therapeutic antitumor immunity J Immunol 1999 162: 144–151
CAS PubMed Google Scholar - Arthur JF et al. A comparison of gene transfer methods in human dendritic cells Cancer Gene Ther 1997 4: 17–25
CAS PubMed Google Scholar - Labeur MS et al. Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage J Immunol 1999 162: 168–175
CAS PubMed Google Scholar - Mackey MF et al. Dendritic cells require maturation via CD40 to generate protective antitumor immunity J Immunol 1998 161: 2094–2098
CAS PubMed Google Scholar - Brossart P et al. Generation of functional human dendritic cells from adherent peripheral blood monocytes by CD40 ligation in the absence of granulocyte–macrophage colony-stimulating factor Blood 1998 92: 4238–4247
CAS PubMed Google Scholar - Tillman BW et al. Maturation of dendritic cells accompanies high-efficiency gene transfer by a CD40-targeted adenoviral vector J Immunol 1999 162: 6378–6383
CAS PubMed Google Scholar - Diao J et al. Human PBMC-derived dendritic cells transduced with adenovirus vector induce cytotoxic T-lymphocyte responses against vector-encoded antigen in vitro Gene Therapy 1999 6: 845–849
Article CAS PubMed Google Scholar - Hardy S et al. Construction of adenovirus vectors through Cre–lox recombination J Virol 1997 71: 1842–1849
CAS PubMed PubMed Central Google Scholar
Acknowledgements
This work was supported by grants No. SFB-432 (to AE) and Tu90/2-1 (to TT) from the Deutsche Forschungsgemeinschaft.
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- H Jonuleit and T Tüting: The first two authors contributed equally
Authors and Affiliations
- Department of Dermatology, J Gutenberg-University, Langenbeckstrasse 1, Mainz, D-55101, Germany
H Jonuleit, T Tüting, J Steitz, J Brück, A Giesecke, K Steinbrink, J Knop & A H Enk
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Jonuleit, H., Tüting, T., Steitz, J. et al. Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity.Gene Ther 7, 249–254 (2000). https://doi.org/10.1038/sj.gt.3301077
- Received: 19 July 1999
- Accepted: 27 September 1999
- Published: 17 February 2000
- Issue Date: 01 February 2000
- DOI: https://doi.org/10.1038/sj.gt.3301077